16-methyl-17-amino-androstane



United States Patent 3,153,063 16=1VETHYL17-AMWO=ANDR$STANE Pietro deRuggieri, iiarmelo Gandolfi, and Domenico Chiaramonti, Milan, Italy,assignors to Qrmonoterapia Richter S.p.A., Milan, ltaly, a corporationof Italy No Drawing. Filed Nov. 13, 1962, Sen. Noe 237,353

Claims priority, application Italy May 30, 1961 6 Qlaims. (Cl.260-397.5)

The present invention relates to compounds of the general formula:

NH: /C W CH3 6 Where R is a member of the group consisting of hydrogenand a lower alkanoyl radical, such as an acetyl radical and the bondbetween carbon atoms 5 and 6 is either a single or a double bond. If thebond is single, the hydrogen atom at position 5 is (Jr-orientated.

These amines are useful as intermediates for the preparation ofphysiologically active hormones, and are, per so, active on the centralnervous system, acting as hypotensive agents because of theirganglioplegic activity. They are prepared from the correspondingalkoxy-ethylideneamino derivatives obtained according to copending U.S.patent application Serial No. 75,091, filed December 12, 1960 and nowabandoned. The method includes the reduction of 16-methyl-17B-('1alkoxy-ethylidene-amino)- androstanes with sodium or zinc amalgam inacid medium to give the corresponding 16-methy1-l7 8-amino-androstanes.

The following examples serve to illustrate the present invention but arenot to be construed as limiting the same:

EXAMPLE 1 16ot-Methyl-17/3-Amin0-3B-Acetoxy-Su-Androsfane 1 part of313-acetoxy-16ot-methyl-17B-(1'-ethoxy-ethylidene amino) Sa androstanemelting point 155-157 C. (see patent application Serial No. 75,091) wasdissolved in 30 parts of tetrahydrofur-ane and 20 par-ts of 3 N HCl. At5-10" 0, 20 parts of 5% sodium amalgam Were added and the reactionmixture was maintained at 510 C. for 3 hours with stirring. Theresulting mixture was decanted from the mercury, diluted with 100 partsof water and made alkaline with NaOH. The precipitated product, filteredand recrystallized from methanol melts at 135- 137 C.; [a] (chloroform).

EXAMPLE 2 1 6 oc-M ethyl-1 7p-Amino-5a-A ndrostane-IiB-Ol A zinc amalgamwas prepared by agitating for 5 minutes a mixture of 32 parts ofpowdered zinc, 3.2 parts of HgCl 1.6 parts of concentrated H01 and 64parts of water and then decanting. The zinc amalgam was suspended bystirring in 24 parts of water, 60 parts of tetra- 3,153,063 PatentedGot, 13, 1964 hydroiurane and 32 parts or concentrated HCI cooled to 5C. and then there was added 8 parts of wot-methyl- 17B (1ethoxy-ethylidene-amino) S-a-androstane-SB-ol, melting point 157-159 C.(see patent application Serial No. 75,091) dissolved in 120 parts oftetrahydrofurane and 8 parts of 4 N HCl. The mixture was then refluxedfor 8 hours, adding 5 parts of concentrated HCl every hour. After theresulting mixture was cooled and made alkaline, it was extracted withchloroform, washed with water and the solvent evaporated. Ihe residuewas recrystallized from methanol to give 6.1 parts of16a-methyl-1-7fl-anrino- Sa-androstane-Bfl-ol melting at 161-163 C.; [a]=-1O (chloroform) By using one of the methods of Examples 1 and 2, andstarting with16m-methy1-17}3-(1'-ethoxy-ethylideneamino)-androst-5-en-3fi-ol (seeapplication Serial No. 75,- 091), there is obtained16a-methyl-175*amino-androst-S- ene-3,B-ol melting at 168-17 1 C.; [u](chloroform).

Starting with16p3-methyl-l7fi-(1'-ethoxy-ethylideneamino)-androst-5-en-3fi-ol (seeapplication Serial No. 75,- 091), there is obtained 16o-methyl-l7fl-amino-androst-5- en-3B-o1 melting at 194-196 C.; [a] =13(chloroform).

Starting with16;8-methyl-17fl-(1-etl1oxy-ethylideneamino)-5a-androstane-3fi-ol (seeapplication Serial No. 75,091), there is obtained 16fi-methyl17fl-amin0-5uandrostane-Zl/i-ol melting at 228-231 C.; [a] =+9(chloroform) The present application is a continuation-in-part of ourcopending application Serial No. 123,091, filed July 11, 1961 and nowabandoned.

We claim:

1. The compounds of the formula wherein X is a member selected from thegroup consisting of Roi and R0 {1] References Cited in the file of thispatent Schmidt-Thome: Chemical Abstracts, vol. 48, November 1954, par.13,738 13-11.

Nomine et al.: Tetrahedron (1960), pages 217, 220.

1. THE COMPOUND OF THE FORMULA